The weaver mutation results in the extensive death of midline cerebellar granule cells. The mutation consists of a single base pair substitution of the gene encoding the G-protein-activated inwardly rectifying potassium channel protein, GIRK2. The functional consequences of this mutation are still in dispute. In this study we demonstrate the in vivo and in vitro rescue of weaver granule cells w...

A single amino acid mutation (G156S) in the putative pore-forming region of the G protein-sensitive, inwardly rectifying K(+) channel subunit, GIRK2, renders the conductance constitutively active and nonselective for monovalent cations. The mutant channel subunit (GIRK2wv) causes the pleiotropic weaver disease in mice, which is characterized by the selective vulnerability of cerebellar granule ...

The phenotype of substantia nigra (SN) neurons in homozygous weaver (wv/wv) mice was studied by combining patch-clamp and single-cell RT-multiplex PCR techniques in midbrain slices of 14-d-old mice. In contrast to GABAergic SN neurons, which were unaffected in homozygous weaver mice (wv/wv), dopaminergic SN neurons possessed a dramatically altered phenotype with a depolarized membrane potential...

We have used sulfhydryl-modifying reagents to investigate the regulation of G-protein-activated inward rectifier potassium (GIRK) channels via their cytoplasmic domains. Modification of either the conserved N-terminal cysteines (GIRK1C53 and GIRK2C65) or the middle C-terminal cysteines (GIRK1C310 and GIRK2C321) independently inhibited GIRK1/GIRK2 heteromeric channels. With the exception of GIRK...